linagliptin

Background: Linagliptin is an anti-diabetic drug that claims no adverse effects and treatment of gestational diabetes mellitus (GDM) demands a safe anti-diabetic medication. Therefore, this study investigates the anti-diabetic efficacy of linagliptin in an induced GDM.Materials and methods: Thirty-two matured female rats (100 - 200 g) were utilized. Sixteen non-pregnant/diabetic animals were fed with a normal diet and sixteen rats were fed with a high-fat (HFD), mated at the estrous stage in 2:1, and pregnancy was confirmed with a spermatozoa in a vaginal smear. The pregnant rats were intraperitoneally injected with a single dose (30 mg/kgb. wt)of streptozotocin (STZ) to induce GDM. The animals were grouped into 4 groups, 8 rats/groups. Group I: control; Group II: control + 10 mg/kgb.wt linagliptin; Group III: GDM; Group IV: GDM + 10 mg/kgb.wt linagliptin. The animals were sacrificed after 14 days of treatment. Blood samples were collected for biochemical parameters.Results: Fasting blood glucose (FBG) insulin, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), malondialdehyde (MDA), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels significant (p < 0.05) elevated in GDM rats, with significant reduction in high-density lipoprotein-cholesterol (HDL-C), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH). Linagliptin administration significantly (p < 0.05) decreased the FBG, insulin, HbA1c, TC, TG, LDL-C, MDA, IL-6, IL-1β, and TNF-α and ameliorates the HDL-C, CAT, SOD, and GSH levels significantly.Conclusion: Linagliptin remarkably showed anti-hyperglycemic, anti-oxidative, and anti-inflammatory properties. Linagliptin could be a promising drug for hyperglycemia treatment during gestation.

Background: Monotherapy for liver dysfunction in diabetes is less effective. This study investigated the effect of combined linagliptin and metformin therapy on liver function in diabetic rats. Methods and materials: Sixty-four matured male (200-300 g) Wistar rats were used. Diabetes was induced with 35 mg/kb.wt streptozotocin injected intraperitoneally. The rats were grouped into eight groups (n = 8). Group I: control; Group II: control + 10 mg/kg body weight linagliptin; Group III: control + 200 mg/kg body weight metformin; Group IV; control + 10 mg/kg body weight linagliptin + 200 mg/kg body weight metformin; Group V: diabetic; Group VI: diabetic + 10 mg/kg body weight linagliptin; Group VII: diabetic + 200 mg/kg body weight metformin; Group VIII: diabetic + 10 mg/kg body weight linagliptin + 200 mg/kg body weight metformin. After the animal was sacrificed, blood and liver samples were collected for biochemical assay. Results: Insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-cholesterol), liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, pyruvate kinase, glucose-6-phosphatase dehydrogenase, malondialdehyde and inflammatory makers increased (p < 0.05) significantly. High-density lipoprotein-cholesterol (HDL-cholesterol), liver antioxidant, glycogen, and glycogen synthase were reduced significantly in diabetic rats. Linagliptin and metformin administration single and combined reduced the insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, pyruvate kinase, glucose-6-phosphatase dehydrogenase, malondialdehyde, inflammatory makers and increased the HDL-cholesterol, liver antioxidant, glycogen and glycogen synthase in diabetic rats.Conclusion: Linagliptin monotherapy alone efficiently controls hyperglycemia and remarkably improves liver functions. Combining linagliptin and metformin could be used as safe and effective therapy for liver dysfunction progression in diabetes.